EGFR Inhibition in EGFR-Amplified Advanced Gastroesophageal Cancer

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As reported in the Journal of Clinical Oncology by Maron et al, a retrospective study found that use of EGFR inhibitor therapy was associated with benefit in patients with unresectable or metastatic EGFR-amplified gastroesophageal adenocarcinoma.

As stated by the investigators, “Subset analyses from phase III evaluation of EGFR inhibition suggest improved outcomes in patients with EGFR-amplified gastroesophageal adenocarcinoma, but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFR inhibition in the largest cohort of patients with EGFR-amplified gastroesophageal adenocarcinoma to date.”

Study Details

A total of 60 patients from 15 centers in six countries met the inclusion criteria for the study. Patients had to have histologically confirmed gastroesophageal adenocarcinoma in the metastatic or unresectable setting, with EGFR amplification identified by using a Clinical Laboratory Improvement Amendments–approved assay; patients also had received on- or off-protocol EGFR inhibitor therapy. Testing could be by tissue next-generation sequencing, plasma circulating tumor DNA next-generation sequencing, or fluorescence in situ hybridization performed by a Clinical Laboratory Improvement Amendments–approved laboratory.

Treatment patterns and outcomes were also assessed in a cohort of 182 patients (6.8% of 2,662 patients with diagnosis of advanced gastroesophageal adenocarcinoma) from a Flatiron Health–Foundation Medicine de-identified clinicogenomic database who had gastroesophageal adenocarcinoma samples showing EGFR amplification.  

Key Findings

Among the 60 patients in the EGFR inhibition cohort, 19 (32%), 15 (25%), 8 (13%), and 18 (32%) received an EGFR inhibitor in first-, second-, third-, and fourth-line or later therapy. Overall, 31 patients (52%) received an EGFR inhibitor with chemotherapy.

Among 56 patients evaluable for radiographic response, objective response was observed in 24 (43%), including 16 (57%) of 28 receiving an EGFR inhibitor with chemotherapy and 8 (29%) of 28 receiving an EGFR inhibitor alone. Objective response was observed in 11 (65%) of 17 receiving first-line treatment (including 9 of 14 receiving an EGFR inhibitor plus chemotherapy and 2 of 3 receiving an EGFR inhibitor alone), 7 (43%) of 15 receiving second-line treatment (5 of 10 and 2 of 5, respectively), 2 (25%) of 8 receiving third-line treatment (0 of 1 and 2 of 7, respectively), and 4 (25%) of 16 receiving  fourth-line or later treatment (2 of 3 and 2 of 13, respectively).

Median progression-free survival was 6.9 months (95% confidence interval [CI] = 6.0–14.3 months), 5.2 months (95% CI = 3.5 months­­–not reached), 6.6 months (95% CI = 2.0 months–not reached), and 2.3 months (95% CI = 1.8–5.0 months) in first-, second-, third-, and fourth-line or later treatment.

Median overall survival was 20.6 months (95% CI = 13.5 months–not reached), 9 months (95% CI = 7.9 months–not reached), 8.4 months (7.6 months–not reached), and 4.2 months (95% CI = 3.4–7.6 months) in first-, second-, third-, and fourth-line or later treatment.

In the clinicogenomic database cohort of 186 patients, only 5% received EGFR inhibitor treatment. Median overall survival in patients receiving first-line treatment was 11.2 months (95% CI = 8.7–14.2)—well below the 20.6 months achieved in the first-line setting in the EGFR inhibition cohort. Median overall survival with second-line treatment in the clinicogenomic database cohort was 8.7 months (95% CI = 6.9–11.8 months).

The investigators concluded, “Patients with EGFR-amplified gastroesophageal adenocarcinoma derive significant benefit from EGFR inhibition. Further prospective investigation of EGFR inhibition in a well-selected patient population is ongoing in an upcoming trial of amivantamab in EGFR- and/or MET-amplified gastroesophageal adenocarcinoma.”

Steven B. Maron, MD, MSc, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Cancer Institute grants. For full disclosures of the study authors, visit


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